Etiology and prognosis of spondyloarthropathies using family-based epidemiological methods

The spondyloarthropathies (SpA) are a group of chronic inflammatory diseases that share several disease characteristics such as inflammation of entheses and extramusculoskeletal manifestations like uveitis, psoriasis, and inflammatory bowel disease. These diseases, or symptoms thereof, are also known to run in families. The purpose of this thesis was to expand knowledge concerning the etiology and prognosis of SpA, using family-based epidemiological methods on data from Swedish health and population registers. In study I, we estimated the familial aggregation of a specific SpA subtype, ankylosing spondylitis (AS), in a nested case-control study of AS cases, population controls, and first-degree relatives of both groups. We were able to provide a precise estimate of the familial aggregation, corresponding to a 20-fold increased risk of AS among first-degree relatives of AS cases. We also estimated the heritability of AS to 77%, i.e. the proportion of susceptibility to AS in the population that is due to genetics. Our estimate can be seen as an upper limit for the heritability, as shared environmental effects were not considered. While both estimates are relatively high, they are lower than previous reports for AS, which have been based on small and often selected samples. In study II, a cohort study, we investigated whether family history of SpA, or its specific subtypes, were predictive of response to treatment with tumor necrosis factor inhibitors (TNFi) in patients with SpA. Despite being such a strong risk factor for disease development, we did not find family history to be associated with prognosis in terms of TNFi drug survival or treatment response at three or twelve months. In study III, we studied temporal trends in pregnancy outcomes among women with axial SpA. We found that women with axial SpA, compared to women from the general population, were at increased risk of pre-eclampsia, preterm birth, and serious infection in the infant. The proportion of cesarean deliveries was also significantly higher among women with axial SpA. The risks had, however, diminished over the last decade, to reach similar levels as in the general population, while the use of effective treatment in the form of TNFi increased before and during pregnancy over the same period. In study IV, we searched for environmental risk factors for AS, with a focus on perinatal characteristics and infections in childhood. In this nested case-control study, we found that having older siblings and a history of tonsillectomy in childhood were associated with AS in adulthood, even after adjustment for childhood socio-economic status and other family-shared confounders through a sibling comparison. By using data from national registers, we were able to perform the hitherto largest studies on these topics regarding etiology and prognosis of SpA. While the genetic influence is substantial in AS, there is a larger contribution of environmental risk factors than previously known. These seem partly related to early life, with a possible influence of childhood infections. We have also added to a growing body of evidence supporting the use of effective treatment in women with axial SpA, before and at least in the beginning of pregnancy, to minimize the risks active that SpA disease pose on pregnancy outcomes

Association of childhood infections and perinatal factors with ankylosing spondylitis: a Swedish nationwide case–control and sibling study

Objectives To identify perinatal and early-life risk factors for ankylosing spondylitis (AS), controlling for family-shared confounding with a sibling comparison design.Methods In this nationwide, register-based case–control study, we identified 5612 AS cases from the Swedish National Patient Register, and matched them with 22 042 individuals without inflammatory arthritis from the general population. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of AS in relation to childhood infections and a broad range of perinatal factors including fetal growth. Significant associations were further tested in a sibling comparison analysis, including 3965 patients with AS and their 6070 siblings without a diagnosis of spondyloarthritis.Results We found no statistically significant associations between any studied fetal growth-related factor or other perinatal factors and the risk of developing AS. In contrast, having older siblings (adjusted OR 1.12; 95% CI 1.04 to 1.22 for one vs no older sibling) and history of a childhood tonsillectomy (adjusted OR 1.30; 95% CI 1.13 to 1.49) were associated with AS in the case–control analysis, results that also held in the sibling comparison. Serious childhood infection and multiple birth were significantly associated with AS in the case–control sample, but estimates were attenuated in the sibling comparison.Conclusions Having older siblings and a history of tonsillectomy in childhood were independently associated with development of AS, even after adjustment for family-shared factors in a sibling comparison analysis. This strengthens the hypothesis that childhood infections play a role in the aetiology of AS

Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice : Results from the ARTIS programme

Objective Longitudinal clinical registry-infrastructures such as Anti-Rheumatic Therapies in Sweden (ARTIS) allow simultaneous comparison of the safety of individual immunomodulatory drugs used in clinical practice, with consistent definitions of treatment cohorts, follow-up and outcomes. Our objective was to assess and compare incidence rates of key safety outcomes for individual targeted synthetic or biological disease-modifying antirheumatic drugs (b/ts DMARDs) in rheumatoid arthritis (RA), updating previous reports and including newer treatments including Janus Kinase inhibitors (JAKi). Methods Nationwide register-based cohort study including all patients with RA in Sweden registered as starting any b/tsDMARD 1 January 2010 through 31 December 2020, followed until 30 June 2021 (N=20 117). The incidence rates of selected outcomes, identified through national healthcare registers, were compared between individual b/tsDMARDs, adjusted for confounding by demographics, RA disease characteristics and comorbidity. Results There were marked differences in treatment discontinuations due to adverse events (rates per 1000 person-years ranged from 18 on rituximab to 57 on tofacitinib), but few significant differences were observed for the serious adverse events under study. Neither cardiovascular events nor general serious infections were more frequent on baricitinib or tofacitinib versus bDMARDs, but JAKi were associated with higher rates of hospital-treated herpes zoster (HR vs etanercept, 3.82 (95% CI 2.05 to 7.09) and 4.00 (1.59 to 10.06)). Low number of events limited some comparisons, in particular for sarilumab and tofacitinib. Conclusion Data from ARTIS supports that the b/tsDMARDs currently used to treat RA have acceptable and largely similar safety profiles, but differences exist in particular concerning tolerability and specific infection risks

Comparison of FBAT, RBT, SAT Coombs IgG and LFA in the 825 sera.

<p>Comparison of FBAT, RBT, SAT Coombs IgG and LFA in the 825 sera.</p

Comparative results for test positive on RBT, LFA, SAT and Coombs.

<p>Comparative results for test positive on RBT, LFA, SAT and Coombs.</p

A continent-wide detailed geological map dataset of Antarctica

Abstract A dataset to describe exposed bedrock and surficial geology of Antarctica has been constructed by the GeoMAP Action Group of the Scientific Committee on Antarctic Research (SCAR) and GNS Science. Our group captured existing geological map data into a geographic information system (GIS), refined its spatial reliability, harmonised classification, and improved representation of glacial sequences and geomorphology, thereby creating a comprehensive and coherent representation of Antarctic geology. A total of 99,080 polygons were unified for depicting geology at 1:250,000 scale, but locally there are some areas with higher spatial resolution. Geological unit definition is based on a mixed chronostratigraphic- and lithostratigraphic-based classification. Description of rock and moraine polygons employs the international Geoscience Markup Language (GeoSciML) data protocols to provide attribute-rich and queryable information, including bibliographic links to 589 source maps and scientific literature. GeoMAP is the first detailed geological map dataset covering all of Antarctica. It depicts ‘known geology’ of rock exposures rather than ‘interpreted’ sub-ice features and is suitable for continent-wide perspectives and cross-discipline interrogation

The GeoMAP (v.2022-08) continent-wide detailed geological dataset of Antarctica

A dataset describing exposed bedrock and surficial geology of Antarctica constructed by the GeoMAP Action Group of SCAR (The Scientific Committee on Antarctic Research) and GNS Science, New Zealand. Legacy geological map data have been captured into a geographic information system (GIS), refining its spatial reliability, harmonising classification, then improving representation of glacial sequences and geomorphology. A total 99,080 polygons have been unified for depicting geology at 1:250,000 scale, but locally there are some areas with higher spatial precision. Geological definition in GeoMAP v.2022-08 is founded on a mixed chronostratigraphic- and lithostratigraphic-based classification. Description of rock and moraine polygons employs international GeoSciML data protocols to provide attribute-rich and queriable data; including bibliographic links to 589 source maps and scientific literature. Data are provided under CC-BY License as zipped ArcGIS geodatabase, QGIS geopackage or GoogleEarth kmz files. GeoMAP is the first detailed geological dataset covering all of Antarctica. GeoMAP depicts 'known geology' of rock exposures rather than 'interpreted' sub-ice features and is suitable for continent-wide perspectives and cross-discipline interrogation